1. Technical Field
Aspects of the disclosure are generally related to compositions and methods for modulating autoantigen expression, more particularly to green tea polyphenol compositions and methods of their use, for example in the treatment or prophylaxis of autoimmune disorders.
2. Related Art
The prevalence of autoimmune disorders in the United States is estimate at more than 8.5 million. Autoimmune reactions can cause inflammation and apoptosis of target cells, leading to destruction of multiple tissues and organs. Patients with autoimmune diseases develop autoantibodies against a diverse group of macromolecules involved in normal functions. For example, anti-SS-A/Ro and anti-SS-B/La autoantibodies are primary markers for certain autoimmune diseases such as lupus erythematosus and Sjögren's syndrome. Existing treatments of autoimmune diseases have focused on the immune system, not the autoantigens that could trigger or sustain a positive feedback loop of inflammation and apoptosis.
Lupus Autoimmune Disorders
Lupus is one of more than 60 types of autoimmune disorders, and is one of the most destructive. Clinical classification of lupus includes systematic lupus erythematosus (SLE), discoid lupus ecrythematosus (DLE), subacute cutaneous lupus (SCLE), drug induced lupus, and neonatal lupus. SLE is the most prevalent form and may affect, multiple tissues such as joints, skin, kidneys, heart, lungs, blood vessels, and brain. It affects mostly young females of childbearing age. Lupus can cause severe joint and muscle pain, extreme exhaustion, fevers, and skin rashes, and can lead to organ failure, scars and death. The skin manifestations of S LE arid DLE are slightly different. DLE affects mainly the skin and the oral cavity with disk-shaped lesions while SLE affects multiple organs. Skin manifestations occur in about 25% of SLE patients, with butterfly shaped lesions distributed on the face and ears. It is believed that cutaneous LE affects 14.6 to 68 per 100 000 people (Callen, J. P. (2004) Br J. Dematol. 151(4):731-6).
Sjögren's Syndrome
Sjögren's syndrome (SS) is another autoimmune disorder that affects multiple tissues. Primary SS is associated with lymphocytic infiltrations of the salivary and lacrimal glands and eventual atrophy, leading to a loss of fluid production. The salivary component of SS is defined as xerostomia, with symptoms generally referred to as salivary hypofunction (Daniels, T. E. and Fox, R. I. (1992). Rheum Dis Clin North Am. 18(3):571-89). If not treated, xerostomia may lead to oral complications (Daniels T. E. and Wu, A J. (2000) Calif Dent Assoc. 28(12):933-41). Estimates of the prevalence of SS are affected by the criteria used for diagnosis. However, genuine differences between various regions and communities exist (Fox, R. I. (1997) Clin Lab Med. 17(3):43 1-44; Vitali, C. et al, (2002) Ann Rheum Dis. 61(6):554-8). The world-wide distribution is believed to be 1/2500 (Kang, H. (1993)). In the United States, SS affects approximately 1% of the population (Carsons, S. (2001) Am J Manag Care. 7(14 Suppl):S433-43.24). In China, one regional study with 26,000 subjects suggested the prevalence of primary SS was only 0.03% (Zhang, N. (1995) Chin Med J (Engl). 108(10):787-8). In Japan, the estimated crude prevalence rates for SS were only 1.9 and 25.6 per 100,000 population in males and females, respectively (Yoshida, S. (1999) Nippon Rinsho. 57(2):360-3). A survey conducted by the Japanese Ministry of Health and Welfare indicated the SS prevalence was just 0.06% among females (Miyasaka, N. (1995) Nippon Rinsho. 53(10):2367-70).
As for xerostomia, one study showed that among a group of 1003 Japanese individuals with an average age of 66, about 9.1% experienced dry mouth during eating (Ikebe, K. et al. (2001) Spec Care Dentist. 21(2):52-9), whereas in the United States, one epidemiological study found that in a group of 2481 individuals aged 65-84 years old, 27% reported either dry mouth or dry eyes (Schein, O. D. et al. (1999) Arch Intern Med. 159(12): 1359-63), and another found that dry mouth ranged from 10% among persons over age 50 to 40% for persons over age 65 (Billings R J., et al. (1996) Community Dent Oral Epidemiol. (5):3 12-6). Although precise statistical comparison between the U.S. population and either the Japanese or Chinese population is not available, it is apparent that SS and xerostomia are more prevalent in the U.S. population, particularly amongst the elderly.
SS is not a curable or preventable disease at present, and whether it can be prevented or delayed is unknown. Treatment is generally symptomatic and supportive. For xerostomia and xerophthalmia, artificial lubricants are commonly used as saliva or tear substitutes (Baudouin, C. et al. (2004) Rev Med Interne. 25(5):376-82). In recent years, salivary stimulants, such as pilocarpine and cevimeline, have been approved by the FDA to treat xerostomia (Fox, R. I. (2003) Expert Opin Investing Drugs. 12(2):247-54); Cassolato, S. F. and Turnbull, R. S. (2003) Cerodontology. 20(2):64-77; Porter, S. R. et al. (2004) Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 97(1):28-46). In addition, oral administration of interferon γ (IFN-γ) was effective in improving saliva production in patients with primary SS (Khurshudian, A. V. (2003) Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 95(1):38-44). However, long-term adverse effects have not been evaluated for these therapies.
Thus, there is a need for additional compositions and methods for preventing and treating autoimmune diseases or symptoms associated with such diseases.